Until a short time ago, studies of neurotransmitter receptors in the brain have relied primarily upon neurophysiological techniques. Recently, however biochemical methods for the direct measurement of receptors have become available. We have demonstrated the specific binding of muscarinic receptors using QNB and CD, nicotinic receptors using Naja naja, GABAergic receptors using muscimol, dopamine receptors using spiroperidol and benzodiazepine receptors using fluitrazepam. We have used these ligands as tools in solving some of the problems in neuropharmacology. We have found biochemical receptor alterations in discrete brain regions from postmortem brain samples of persons dying from Huntington's, Parkinson's, Alzeheimer's Disease and from Schizophrenic brain samples. I am interested in finding new ligands in the future so that novel neurotransmitter and drug receptors can be labeled. We are currently identifying the barbiturate and nonbenzodiazepine receptors in brain. An important area of the research involves the mechanism of coupling between the receptor and the effector (perhaps the guanine nucleotide binding site or adenylate cyclase). Other important areas involve receptor regulation and receptor heterogeneity. Neurotransmitter receptors appear to be regulated in an up or down direction depending upon neuronal activity. We are interested in determining the exact mechanism of this regulation. Neurotransmitter receptors for the opiate, alpha- and beta-adrenergic, dopamine, histamine and muscarinic cholinergic systems exist as subtypes. Receptor binding studies have complimented classical pharmacological studies in this respect. We are interested in determining the mechanism of receptor heterogeneity. We have clues which indicate that ions, and guanine nucleotides are important agents in illustrating receptor homogeneity.